Common dosage forms for antibiotic drugs are oral solutions, suspensions, syrups, emulsions, and other liquids. Such dosage forms are particularly important at the extremes of age, i.e. in children and the elderly, who cannot easily swallow pills, tablets, capsules or other solid dosage forms. Unfortunately, many antibiotics which are frequently prescribed, as well as many new antibiotics under development, have a bitter taste to a greater or lesser degree. This bitterness can sometimes be eliminated by use of a salt or ester of the antibiotic, or the bitterness may be overcome by the use of flavorants and/or masking agents in the liquid vehicle of the dosage form. In the case of some antibiotics in the the erythromycin or macrolide category, this bitterness is so pronounced that the usual means of eliminating or masking the undesirable taste are unable to provide a palatable dosage form. As a result, there is a continuing need for novel derivatives of these compounds which are flavorless or which have a much reduced bitter taste.
Creamer, Pharmaceutical Technology, 6(3) (March, 1982), "Organosilicon Chemistry and Its Application in the Manufacture of Pharmaceuticals", printed by the Silicones and Urethane Intermediates Division of Union Carbide Corporation and identified as SUI-185 5/82-2M, describes the use of silylation in producing various drugs and drug intermediates. A detailed bibliography is also provided.
U.S. Pat. No. 2,746,956, "Method of Silylating Organic Comopounds" describes what is claimed to be the synthesis of a silylated erythromycin derivative. The patentee states that a bis-silylated compound was obtained. However, the experimental method of the '956 patent has been repeated and found not to provide the results indicated.
It is an object of this invention to provide novel macrolide antibiotic compounds.
It is another object of this invention to provide antibiotic compounds which are sufficiently flavorless to be used in liquid dosage forms for oral administration.
These and other objects of the invention will be evident from the following disclosure.